Camptothecin (I) is a naturally occurring pyrrolo (3,4-b)-quinoline alkaloid having remarkable antitumour and antileukemic activities (Wall et. al., J. Am. Chem. Soc. 88, 3888, 1966). It acts as an inhibitor of DNA topoisomerase I (Hsiang et al., J. Biol. Chem., 260, 14873, 1985). Two natural analogues of the compound, 9-methoxy camptothecin (II) (Govindachari and Viswanathan, Phytochemistry, 11, 3529, 1972; Wu et al., Phytochemistry, 39, 383, 1995) and 20-O-acetyl camptothecin (III) (Wu et al., Phytochemistry, 39, 383, 1995; Das et al., Indian J. Chem, 36B, 207, 1997) also possess significant cytotoxic property. The decarboxylated E-ring analogues of camptothecin (I) and 9-methoxycamptothecin (II), known as mappicine ketone (nothapodytine B) (IV) and 9-methoxymappicine ketone (nothapodytine A) (V) respectively are also naturally occurring alkaloids (Wu et al., Phytochemistry, 42, 907, 1996; Pendrak et al., J. Org. Chem, 59, 2623, 1994). Mappicine ketone (IV) has recently been identified as an antiviral lead (Pendrak et al., J. Org. Chem., 59, 2623, 1994; J. Org. Chem. 60, 2912, 1995).
As a drug camptothecin (I) itself has several problems including its high toxicity and low water solubility. So several analogues of the compound have been prepared to evaluate their clinical efficacies. Recently different 5-substituted alkoxycamptothecins have been found to exhibit potent anticancer activity (Subrahmanyam et.al., Bioorg. Med, Chem. Lett., 10, 369, 2000). The methods of preparation of 5-alkoxy camptothecins are limited. They were prepared earlier from 5-hydroxycamptothecin which was obtained by treatment of camptothecin with I2 and K2CO3 in DMF. 5-Hydroxycamptothecin was subsequently converted into 5-alkoxycamptothecins by reacting with alcohols in the presence of BF3.OEt2 (Swada et al., Chem. Pharm Bull., 39,2574,1991). This is a two-step process and so the overall yields of 5-alkoxycamptothecins will be diminished. The experimental procedures are also tidious. In the other approach camptothecin was heated with FeCl3-H2SO4 in EtOH for 20 hr to obtain a mixture of 5-ethoxy and 5-hydroxycamptothecins. The mixture was again heated with aqueous HCl for 20 hr to obtain 5-hydroxycamptothecin exclusively. This 5-hydroxycamptothecin was then treated with different alcohols in the presence of p-toluenesulfonic acid to prepare 5-alkoxycamptothecins (Subrahmanyam et al., Biorg. Med. Chem. Lett., 10, 369, 2000). This method involves several steps and the time required is high.